Toxic epidermal necrolysis and Stevens-Johnson syndrome

Harr, Thomas; French, Lars E.

doi:10.1186/1750-1172-5-39

Cited by 512 publications

(671 citation statements)

References 109 publications

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“…Recent molecular advances have led to improved understanding of this relationship. Histologically, a key feature is keratinocyte apoptosis and death resulting in epidermal necrosis and blistering as seen on physical examination [1]. Evidence indicates that the immune system mediates this toxicity.…”

Section: Introductionmentioning

confidence: 99%

Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome

Burkhart

Abernethy

Jackson³

2015

J. Med. Toxicol.

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Drug features that are associated with StevensJohnson syndrome (SJS) have not been fully characterized. A molecular target analysis of the drugs associated with SJS in the FDA Adverse Event Reporting System (FAERS) may contribute to mechanistic insights into SJS pathophysiology. The publicly available version of FAERS was analyzed to identify disproportionality among the molecular targets, metabolizing enzymes, and transporters for drugs associated with SJS. The FAERS in-house version was also analyzed for an internal comparison of the drugs most highly associated with SJS. Cyclooxygenases 1 and 2, carbonic anhydrase 2, and sodium channel 2 alpha were identified as disproportionately associated with SJS. Cytochrome P450 (CYPs) 3A4 and 2C9 are disproportionately represented as metabolizing enzymes of the drugs associated with SJS adverse event reports. Multidrug resistance protein 1 (MRP-1), organic anion transporter 1 (OAT1), and PEPT2 were also identified and are highly associated with the transport of these drugs. A detailed review of the molecular targets identifies important roles for these targets in immune response. The association with CYP metabolizing enzymes suggests that reactive metabolites and oxidative stress may have a contributory role. Drug transporters may enhance intracellular tissue concentrations and also have vital physiologic roles that impact keratinocyte proliferation and survival. Data mining FAERS may be used to hypothesize mechanisms for adverse drug events by identifying molecular targets that are highly associated with druginduced adverse events. The information gained may contribute to systems biology disease models.

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Section: Introductionmentioning

confidence: 99%

Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome

Burkhart

Abernethy

Jackson³

2015

J. Med. Toxicol.

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“…TEN is an acute mucocutaneous eruption that is associated with high mortality, ranging from 25% to 30% [4]. Various drugs that can induce TEN have been reported, and monoclonal antibody drugs as agents responsible for SJS or TEN, including cetuximab and adalimumab, have recently been reported [5,6].…”

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confidence: 99%

Late onset toxic epidermal necrolysis induced by mogamulizumab, an anti‐CC chemokine receptor 4 antibody for the treatment of adult T‐cell leukaemia/lymphoma

Shiratori

Ohhigashi

Ito

et al. 2015

Hematological Oncology

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Late onset toxic epidermal necrolysis induced by mogamulizumab, an anti-CC chemokine receptor 4 antibody for the treatment of adult T-cell leukaemia/lymphomaTo the Editor Adult T-cell leukaemia/lymphoma (ATLL) is a rare type of highly aggressive peripheral T-cell malignancy induced by infection with human T-cell leukaemia virus type 1 (HTLV-1) [1]. Acute and lymphoma types of ATLL particularly display an aggressive clinical course with a poor outcome because of the resistance to conventional combination chemotherapies [2]. Mogamulizumab (MOG), a defucosylated humanized monoclonal antibody targeting CC chemokine receptor 4 (CCR4), has recently been launched for treatment of ATLL; almost all ATLL cells express CCR4 [3]. On the other hand, skin rashes have been reported as significant adverse effects of MOG [3]. It is often difficult to distinguish between a skin lesion caused by MOG and an ATLL lesion, and the detail characteristics, clinical course and treatment are still unclear, particularly in severe events including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Here, we report a case of TEN induced by MOG for the treatment of ATLL, which developed at a very late phase after the last infusion of MOG.A 77-year-old man was introduced to our hospital for general fatigue, palpitation and abnormal lymphocytes in peripheral blood. He was diagnosed as having acute type of ATLL by flow cytometry analysis and detection of HTLV-1 antibody. He received low-dose etoposide as an initial treatment; however, lung infiltration of ATLL cells was demonstrated by bronchoalveolar lavage and transbronchial lung biopsy 7 months after diagnosis. Because combination chemotherapies were considered to be a high risk for his general condition, MOG monotherapy was started for 8 months. Detail clinical course of the patient following the treatment of MOG was shown in Figure 1. At the initial infusion of MOG, an infusion reaction was diagnosed for the rapid development of respiratory failure, hyperthermia and systemic skin rash. Three courses of MOG monotherapy were given in combination with a steroid, and MOG was then discontinued owing to a grade 4 adverse effect of thrombocytopenia. He achieved complete remission in both peripheral blood and lung lesions after the therapy. Serum soluble interleukin-2 receptor levels were also significantly decreased from 6290 to 1190 U/ml. On day 5 after the last infusion of MOG, he developed systemic erythema. The skin lesions were improved by administration of 1 mg/kg of prednisolone; however, it was exacerbated again during the tapering of prednisolone. The results of a skin biopsy on day 30 after the last infusion of MOG were consistent with a drug eruption rather than an ATLL lesion. We increased the level prednisolone; however, the lesions continued to progress. On day 42 after the last infusion of MOG, a total of 25% of epidermal necrolysis and erosion, enanthema of the scrotum and systemic symptoms including fever had developed [ Figure 2(A) and (B)], leading to the diagnosis ...

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“…Although similar histopathologically to TEN, SJS needs at least two mucous membrane involvements, and unlike TEN, the skin involvement is generally limited to less than 30% body surface area. Skin biopsy can rapidly differentiate between SSSS and TEN/SJS 4.…”

Section: Discussionmentioning

confidence: 99%

Severe case of staphylococcal scalded skin syndrome in a 5‐year‐old child – case report

Aydin

Alsbjørn

2016

Clinical Case Reports

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Toxic epidermal necrolysis and Stevens-Johnson syndrome

Cited by 512 publications

References 109 publications

Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome

Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome

Late onset toxic epidermal necrolysis induced by mogamulizumab, an anti‐CC chemokine receptor 4 antibody for the treatment of adult T‐cell leukaemia/lymphoma

Severe case of staphylococcal scalded skin syndrome in a 5‐year‐old child – case report

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